Thursday, September 25, 2008

ScienceDaily (Sep. 24, 2008) — Calorie restriction, a diet that is low in calories and high in nutrition, may not be as effective at extending life in people as it is in rodents, according to scientists at Washington University School of Medicine in St. Louis.

Previous research had shown that laboratory animals given 30 percent to 50 percent less food can live up to 50 percent longer. Because of those findings, some people have adopted calorie restriction in the hope that they can lengthen their lives. But the new research suggests the diet may not have the desired effect unless people on calorie restriction also pay attention to their protein intake.

In an article published online this month in the journal Aging Cell, investigators point to a discrepancy between humans and animals on calorie restriction. In the majority of the animal models of longevity, extended lifespan involves pathways related to a growth factor called IGF-1 (insulin-like growth factor-1), which is produced primarily in the liver. Production is stimulated by growth hormone and can be reduced by fasting or by insensitivity to growth hormone. In calorie-restricted animals, levels of circulating IGF-1 decline between 30 percent and 40 percent.

"We looked at IGF-1 in humans doing calorie restriction," says first author Luigi Fontana, M.D., Ph.D., assistant professor of medicine at Washington University and an investigator at the Istituto Superiore di Sanità in Rome, Italy. "For years, we have been following a cohort of people from the CR Society who have been on long-term calorie restriction. We found no difference in IGF-1 levels between people on calorie restriction and those who are not."

The CR Society members, who call themselves CRONies (Calorie Restriction with Optimal Nutrition), had been on a calorie-restriction diet for an average of seven years when Fontana did the measurements, but their IGF-1 levels were virtually identical to sedentary people who ate a standard, Western diet.

Because calorie restriction is linked to extraordinary increases in maximal lifespan in rats and mice, Fontana and colleagues at Washington University, including principal investigator John O. Holloszy, M.D., professor of medicine, have been involved in a scientific study that compares calorie restriction to exercise and measures many biological factors linked to longevity and health. Called the CALERIE study (Comprehensive Assessment of the Long term Effects of Reducing Intake of Energy), the project randomly divided 48 people into three groups: Eighteen cut their caloric intake by 25 percent for one year. Another 18 started exercising to increase their energy expenditure by 25 percent for a year. A third group of 10 people didn't change anything.

At the end of that year, the investigators measured IGF-1 levels in all three groups. Again they found no reductions in the group on calorie restriction.

"That was puzzling because it was the first time we hadn't seen agreement between mice and rats on calorie restriction and humans on calorie restriction," Fontana explains. "But we know there are two major influences on IGF-1 levels: calorie intake and protein intake. So we decided to look at the influence of protein."

Again, Fontana had a ready-made study group. His team has been following a population of strict vegans for several years. They tend to eat less protein than the CRONies from the CR Society, so he compared IGF-1 levels between the two groups.

"The vegans had significantly less circulating IGF-1, even if they were heavier and had more body fat than CRONies," he says. "Protein in the diet seemed to correlate with the lower levels of IGF-1. The strict vegans took in about 10 percent of their total calories from protein, whereas those on calorie restriction tended to get about 23 or 24 percent of calories from protein."

The investigators wanted to take one more look at the relationship between dietary protein and IGF-1, so Fontana asked a group of CRONies to eat less protein for a few weeks. He says it was not easy to cut protein because those on calorie restriction have to do a lot of calculating and juggling to ensure they take in very few calories and still get adequate nutrition. Increasing dietary protein is one way many CRONies guard against becoming malnourished.

"But six of them agreed to lower their protein intake," Fontana explains, "and after three weeks their circulating IGF-1 declined dramatically."

Previous research from Fontana's group had found that a diet lower in protein might protect against some cancers. These more recent findings suggest lowering protein also might be important to longevity. Fontana admits his evidence is preliminary, but the findings suggest that when people adjust their diets to improve health and lengthen life, they should control not only calories and fat but also keep an eye on protein.

Fontana isn't proposing radical low-protein diets. Instead, he is suggesting the current recommended daily allowance (RDA) for protein, which is 0.82 grams of protein per kilogram of body weight, or about 56 grams of protein for an average, adult man and 46 grams for an average, adult woman. Most people, including CRONies, consume much more protein than the RDA recommendation.

"It's much easier to restrict protein than to restrict calories," he says. "If our research is on the right track, maybe humans don't need to be so calorie restricted. Limiting protein intake to .7 or .8 grams per kilogram per day might be more effective. That's just a hypothesis. We have to confirm it in future studies."

Until then, Fontana suggests people might want to look at protein consumption and tailor it to RDA recommendations. Traditionally, he says, nutritionists have not worried about people eating too much protein, but these findings suggest perhaps they should.

Adapted from materials provided by Washington University School of Medicine, via EurekAlert!, a service of AAAS

* * *

I still have to look at the papers to see whether the majority of non-vegans' protein was coming from animal products, or if excessive plant protein can induce high IGF-1 as well. If not, this research dovetails nicely with prior studies showing protein, and, more specifically, methionine restriction increase lifespan.

Marion Higgins is very good at remembering. She remembers writing her first book 10 years ago. She remembers moving into Seal Beach’s Leisure World in 1989. She remembers the history of furniture acquired at long-ago garage sales and celebrating the end of the World War – both II and I. She remembers hearing the Titanic had just sunk, and the long railroad ride to her family’s homestead in a new state called Idaho. And she remembers hating sunbonnets.

That would have been in the ’90s – the 1890s.

Mrs. Higgins turns 112 on Sunday. She is the oldest living Californian and is believed to be the 21st oldest living human. She belongs to an exclusive but growing population of super-old folks whose longevity is so much more than a family bragging rite.Her life has spanned the terms of 20 of the 43 presidents in U.S. history. Her frail body, sharp-as-a-tack mind and amazing longevity are being closely studied by a little-known Los Angeles research center to discover secrets to living long and well.

According to the Gerontology Research Group at UCLA, the average life expectancy for Americans born today is 77.6 years (80.1 for women and 74.8 for men). The 2000 census found some 50,000 Americans who claimed to have reached 100.

The research group, accepted as a global authority on the super-elderly by Guinness World Records, among others, doesn’t care about those who’ve merely crossed the 100-year mark. These scientists become interested after someone reaches 110 – a super-centenarian – which only about 500 Americans of those 50,000 will.

Then, the group’s network of clever gerontology detectives like Robert Young seeks proof and insights.

“The entire globe has been explored and mapped,” Young says. “Now, we can start discovering the geography of the human life span.”

Young and others mine troves of data to verify the truly old, research their lives and uncover senior frauds. Earlier in life, it seems, adults tend to fib about their age on the low side; the age 39 keeps coming to mind. But somewhere in their late-80s/early-90s, people start padding ages on the high side, encouraged by proud family members and even the odd tourism agency.

In the eyes of these researchers, Marion Higgins is among the verified elite. She’s a living textbook on aging whose lifestyle, habits, health, mental acuity and genes – along with, ultimately, her autopsied body – may offer valuable clues in the age-old search for the secrets of longevity.

“We know so much more than before,” says Dr. L. Stephen Coles, a physician and co-founder of the Gerontology Research Group. “We see some patterns. For instance, your parents’ genes are primary. You don’t ever want to be fat. And optimists seem to fare particularly well. But we’re still only beginning to decipher the biological hieroglyphics of the human genome and how the human body ages.”

To Mrs. Higgins, who’s had 40,907 days to figure it out since June 26, 1893, that’s so much high-falutin’ folderol.

“I face every day one at a time and I’m always learning something new,” she says. “I’m just a slow learner.”

Also, she doesn’t eat raspberries. Not even for birthday celebrations. Mrs. Higgins’ second son, Horace, will preside over the family festivities. He’s 82, played tennis three times a week until last winter and may be the only Caltech graduate to attend a 60th class reunion – and bring his mother.

Super-centenarians remain rare, but their numbers are growing. In 1999, the gerontology group, a loose band of doctors, demographers and part-time researchers, counted 45 people verified as 110 or older. Today, its website (www.grg.org) lists 66. Over the years, it’s documented 835 super-centenarians, including 16 who reached 115.

Young, the group’s senior investigator, says few people have the ambition to reach 110. But, he notes, “At 109, given the alternative, 110 can seem acceptable.”

He estimates the world’s population of super-centenarians at 250 and growing, in part because doctors, medicines and nutrition have prolonged what experts call the human health span – the period between birth and the cascade of medical problems that mark the end of life.

Verification by the research group is a rigorous, peer-reviewed procedure involving original documents such as birth and marriage certificates. Modern reissues of documents or family Bible notations are insufficient.

Young and group colleagues such as Louis Epstein often pore over old census data and military draft records. Many of the 1890 census records were destroyed by fire, but the 1900 census is a treasure chest, listing birth month and year for each resident at most U.S. addresses.

Epstein, the 44-year-old owner of an Internet service provider in Putnam County, N.Y., and Young, a 31-year-old graduate student in Atlanta, share an academic delight in digging up accurate documents, uncovering frauds and challenging each other.

Investing a few hours each day, they work with a network of like-minded researchers around the world who monitor the continued existence of listed super-centenarians and help gather documentation on new ones from slow-moving officials, gullible news media and nonchalant families who do not share the researchers’ diligence, discipline or sense of urgency.

For instance, Young has been waiting months for a marriage certificate from the family of Mary MacIsaac in Saskatchewan that would add her to the list at 111. “You must think and question like a detective,” he says.

Epstein and Young keep a list of false and exaggerated old-age cases. Charlie Smith of Liberia claimed to be 137 but was really only 105. Susie Brunson of South Carolina said she was 123, 18 years older than documents showed. They even uncovered an apparent conspiracy of travel agents on a Caribbean island who touted phony native super-centenarians to promote tourism.

“When claiming to be young becomes futile,” Young notes, “claiming to be older can seem desirable.”

Age 115 is now regarded as a realistic upper limit to human longevity, which five women could reach by November. The oldest documented human was Jean Calment of France, who died Aug. 4, 1997, at 122 years and 164 days. The oldest validated super-centenarian today is Hendrikje Van Andel of the Netherlands, who will turn 115 next week. The oldest American is Elizabeth Bolden of Tennessee, who will turn 115 on Aug. 15.

Why bother with all this?

“First of all,” says Epstein, “facts are important in life. And so is debunking frauds.”

Young, who grew up fascinated by World War I tales told by an aged aunt, thinks there’s much to learn about history from, say, an ancient war veteran or the child of a slave. He travels to birthday parties for listed super-centenarians, where he’s treated like family.

“I want to educate people on what it takes to live a very long time,” he says. “It’s not easy and it’s not a circus sideshow.”

“People think if we can only eliminate disease after disease, we can live forever,” he says. “Not! Our bodies are biological machines with certain warranty periods built in through the DNA of our fathers and mothers. So pick your parents wisely.”

Indeed, the group’s research shows genetics can trump lifestyle. Mrs. Higgins’ siblings lived into their 80s, her mother to 92, and her father to 101. Young’s old notes show that men with sisters living to 100 are 17 times more likely than others to make it that far themselves. Other indicators are less clear.

In the longevity race it’s best to be female; 90% of super-centenarians are women. Coles also sees moderate living as critical. Or as Mrs. Higgins puts it, “I never had enough money to lead a riotous life.”

During World War II, when two sons served in the Navy and a third was a USO entertainer in Les Brown’s Band of Renown, Mrs. Higgins lived in Pomona and made tail de-icers for B-17 bombers. Her husband, John, a machinist, died in 1949 at 60. After a career with the Los Angeles County tax assessor, Mrs. Higgins has drawn Social Security since the first Eisenhower administration.Being active and involved with others also seems to lengthen longevity. Mrs. Higgins set some records in the Senior Olympics in her day, which, she admits, reflects the absence of competitors in her 85-to-90 age bracket 25 years ago.

Her social schedule is built around visitors and visiting, as well as audiobooks (mysteries are a favorite), religious radio programs and garage sales, which she and son Horace visit weekly before they do crossword puzzles together.

He and his wife, Liz, also take dictation of a continuous stream of super-centenarian stories. Many were collected in a book privately published by Mrs. Higgins. She’s sold 900 copies so far at prices that vary according to her estimation of a customer’s willingness to pay.

“In the fifth grade,” Mrs. Higgins recalls, “I got a tablet and sat down to write a book. I was very excited. But I couldn’t write anything because I hadn’t lived much yet. So I waited ‘til I was 102. Writing makes me feel so alive.”

Although no one remains from her early years to contradict details, Mrs. Higgins’ memory seems sharp and clear. She recalls the word games her father invented while the farm family sorted beans around the dining room table. She can still rattle off the alphabet – backward.Mrs. Higgins’ eyesight and hearing have clouded in recent years, but her senses of taste and smell still function. At 96, she had a hip replaced, and she broke her thigh a few years ago after a stumble. “I gave away those shoes,” she says.

That injury caused her Assembly of God minister, Howard Fox, to install a bicycle horn on Mrs. Higgins’ cane. She has also had some facial skin cancers removed, the delayed price for often shucking that sunbonnet behind her mother’s back a century ago.

Moderation in diet also enhances longevity. Coles cites studies of lab animals fed less and living longer than relatives on more bounteous fare. More bluntly, Young adds, “We don’t find any fat 110-year-olds.”

Mrs. Higgins, who awakens about 8 a.m. daily, weighs 134 pounds, up a little since her activity declined in recent years. For breakfast, she has oatmeal and fruit. For lunch, a sandwich, soup and more fruit. And for dinner, her housekeeper knows that chicken or pork chops, broccoli and apple sauce or Mrs. Higgins’ beloved peaches are always welcome.

Her birthday this weekend will not be celebrated with any of those little firecrackers that Mrs. Higgins liked to throw around in packs during countless summer evenings. Nor will there be cake. Instead, she’ll get a blueberry pie and vanilla ice cream. Visitors who want candy know to keep boxes of chocolates beyond her reach.

They also know that at the slightest urging, Mrs. Higgins will accurately recite entire epic poems from her childhood, detailed verse after detailed verse, her weathered fingers still fidgeting with her skirt as they might have in front of that ninth-grade English class 98 years ago.

A visiting Coles marvels aloud at the recitation and the sharp memory of California’s oldest person, taking note of it all for his super-centenarian files.

One of these things doesn’t belong here: Work hard, don’t worry, reflexology, cake and ice cream.

Actually, they were all cited as reasons for longevity at A Centenarian Birthday Celebration at the Dale Association on Wednesday.

• Helen Whitwell, 102; Loraine Clark, 100; Leetah Brown, 104; and Ada Baes, 101, were honored by the Niagara County Office for the Aging and the Niagara County Bicentennial committee. There are 27 people in the county who are 100 years old and some could not attend the centenarian parties.

The Dale Association dining room was filled with family, well-wishers and seniors who come regularly for lunch. There was cake and ice cream for dessert.

• Leetah Brown, who was born in Pennsylvania, was married twice and had no children. During World War II, she worked in an ammunition factory.

“I hauled 4,000 pound of bombs behind me to the shipping room,” she said. “That made me so I don’t fear everything.”

Her secret for longevity: “The Lord made me that way. I haven’t done anything special to keep me older,” she said. “I’ve had a lot of sickness in my life, but I recovered. I’m just tough.”Brown has been practicing and teaching reflexology since 1980. Great niece Debby Dearborn said: “She’s very involved with holistic medicine. That has a lot to do with why she’s lived so long.”

• Ada Baes and Helen Whitwell helped get the Dale Association going. Baes volunteered at the front desk. Helen and Al Whitwell built the snack bar, using wood from a barn.

Baes, a Lockport native, came to the Dale Association after retiring from teaching in Akron for 22 years. She has two sons and enjoys listening to music.

• Helen Whitwell, taught school 35 years in Lockport and Gasport. In 1930, she started a public/private school for families who were not happy with the Lockport schools. She and her husband helped build the Dale Association.

His grandparents had a tavern on Ridge Road that was visited by the Marquis de Lafayette, who ate in the kitchen with the family.Her secret? “She drinks goat milk every day,” said her daughter, Doris Whitwell. “She has for years and years.”

• Loraine Clark’s mother died during childbirth when she was 2. Her father remarried and the family grew to 10 children.

Loraine and Lewis Clark operated Clark’s Charcoal Grill for 23 years. The summer place served grilled foods, but was famous for its homemade pies. “Only eat things that I like,” Loraine said. “I never eat anything I don’t like.”

Hard work has carried her for a century. “We would sell 100-125 pies and make them the same day,” Loraine said. “It was famous. People came from Rochester.”

Loraine and Lewis had four children, and 14 members of the family attended the lunch. One son who lives in Arizona was not in attendance, but did come to her 100th birthday celebration in May.

“She doesn’t worry too much. She lets every day take care of itself,” said son Donald Clark who lives in East Aurora. “She’s our inspiration.”“Attitude is a big thing with her,” daughter Rita McGuinnes. “She’s not a worrier. She very seldom gets stressed out about anything.”

Wednesday, September 17, 2008

At 108, Evanston woman has personal and scientific knowledge about agingShe likes to watch golf, nap and walk—but scientists are interested in her genes

By Deborah Horan | Chicago Tribune reporter September 15, 2008

Evelyn Ralston, 108, lives in Evanston and has a birthday on Oct. 17. If she celebrates just two more birthdays, she'll be a supercentenarian, a person who has made it to 110, an age only 1 in nearly 6 million ever reaches. (Tribune photo by Jose M. Osorio / August 11, 2008)

Scientists would love to study Evelyn Ralston, pepper her with questions about her lifestyle, take samples of her DNA.

Not that their grand endeavors particularly concern the Evanston centenarian. Ralston would rather watch golf on television, nap in the afternoon and take daily walks outside her retirement home, a plush assisted living facility called Mather Place at The Georgian.

"I'm not that interesting," said Ralston, alert and immaculately dressed on a recent afternoon.

At 108 years old, Ralston is not only interesting to gerontologists, she belongs to a selective group of people who have lived more than a century. If she celebrates just two more birthdays, she'll enter an even more exclusive cohort of supercentenarians, people who have made it to 110, an age only 1 in nearly 6 million ever reaches.

Ralston will turn 109 Oct. 17. Her thin frame and unruffled manner likely helped her live this long; scientists say people who live longer tend to be slim and less stressed about life's ups and downs. But those traits are secondary to the attribute that matters: good genes.

"In order to make it past 100, you had to win the genetic lottery at birth," said Jay Olshansky, a professor of epidemiology at the University of Illinois at Chicago.

Gerontologists are discovering that the secret to longevity lies not in a magical Fountain of Youth, but remains hidden—for now—along the intricate genetic sequencing in a person's DNA. The challenge is to map the genomes of the really old to find which gene mutations they have in common.

"Something helps them get to old age," said Nir Barzilai, a professor of medicine at the Albert Einstein College of Medicine in New York, who has been studying centenarians since 1998. "We're trying to identify the genetic elements that help protect them."

So far, he has discovered four genes that he says appear important to longevity: two are related to good cholesterol; one exists in fat—and the less fat the better; the fourth gene delays growth.

The study of the very old has made other gains in recent years, gerontologists said.

Part of the reason is that there are more centenarians than ever before due to medical breakthroughs that reduced child mortality rates, deaths from infectious diseases, and the number of women dying during childbirth. Luck plays a factor too.

"You have to avoid getting run over by a bus," Olshansky said. "Then you have the opportunity to express the longevity potential you were born with."

Thomas Perls, director of the New England Supercentenarian Study and a geriatrician at Boston Medical Center, has found people older than 100 tend to be a diverse group—they may have had heart attacks or smoked or were overweight for part of their lives, and yet something compelled them to live a century.

But after 110, that heterogeneity ceases, he said. He has mapped the DNA of some 80 people over 110 and found they were more genetically homogenous. He hopes that similarity will make it easier to isolate the variations that helped them live so long.

"With [homogeneity] comes a much better chance of discovering some of these genetic variations," Perls said.

In about a year, Ralston would be eligible to participate in Perls' study. Ralston has a baptismal certificate and a passport to prove her age—but verifying even that fact has proved difficult for scientists studying extreme age.

Few places at the turn of the 19th century issued birth certificates. Births, if they were noted at all, were registered in church logs. Many people, gerontologists said, exaggerate their age or don't really know it. The lack of documentation makes keeping statistics difficult.

Data from the Illinois Department of Public Health, for instance, showed a little more than 2,000 people were ages 100 to 104 in 2000, the most recent statistic available. The stats logged 59 as more than 110 years old. Gerontologists said those numbers are likely bloated.

Regardless, Ralston plans a quiet celebration with little fanfare.

If prompted, she'll recount her family's first car, bought in 1926, and the time she drove it off the family farm to help her brothers steer cattle to market.

She remembers her first trip to Europe after she got her passport at age 72.

Public Health Division, National Ageing Research Institute, Melbourne, Australia. i.blackberry@nari.unimelb.edu.au

To identify protective dietary predictors amongst long-lived elderly people (N= 785), the "Food Habits in Later Life "(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.

Sunday, September 14, 2008

International Year of the Older PersonMeet Centenarian - Anais Passe Coutrin

Saturday 4 December 1999

Anais Passe-Coutrin, nee Dolius, was born on August 9, 1896, at Capesterre in Marie-galante. Orphaned from childhood, she was raised by her older sister, Loulouse.

At age 13, Anais left the island of her birth for mainland, Guadeloupe.

At an early age, she began working as a servant in different houses but to this day she has very fond memories of her stay at the Corbins in Morne a l”Eau. Apart from celebrating her 20th birthday there, it was also the year she got married. On October 16, in Moule, Anais married Eloi Passe-Coutrin, a farmer, also from Marie-Galante.

They had seven children, five of whom are still alive. She now has 33 grand children and 53 great-grands. Anais has had a very active life – working the land with her husband, caring for children, working in the market, making “carpate” oil and “gros sirop”. Up to the age of 90, she was still maintaining a kitchen garden. She used to eat the fresh produce of the land and was particularly fond of bananas, manioc with gros sirop from the sugar cane. She does not like rice.

Now, old age does not allow her to enjoy such delicacies any more. She has to eat mainly pureed food prepared by one of her daughters with whom she has been living since the 1970s. After an incident of poisoning, she discovered soya milk, which she prefers over cow’s milk.

During her youth, Anais had no health problems. She had never gone to the doctor. Never had surgery. Now, she only receives a doctor’s visit for flu vaccination. Apart from her reduced mobility, Anais has an exceptional dynamism and physical freshness.

Family and the Lacroix community (the section of Moule where she lives) surround her, and faith holds a special place in her life. Every Friday, she receives blessings from the village priest. A pretty woman, she puts on her toiletries and adorns herself with jewelry on these occasions.

Work, healthy food from the land, faith, uprightness – these are her secrets for longevity. Despite her old age, Anais a.k.a Manna has great lucidity. A woman who provides pleasant company, who does not regret anything from her past, she continues to live peacefully while waiting for, according to her “God’s calling”.

Dietary restriction (DR) lowers mitochondrial reactive oxygen species (ROS) generation and oxidative damage and increases maximum longevity in rodents. Protein restriction (PR) or methionine restriction (MetR), but not lipid or carbohydrate restriction, also cause those kinds of changes. However, previous experiments of MetR were performed only at 80% MetR, and substituting dietary methionine with glutamate in the diet. In order to clarify if MetR can be responsible for the lowered ROS production and oxidative stress induced by standard (40%) DR, Wistar rats were subjected to 40% or 80% MetR without changing other dietary components. It was found that both 40% and 80% MetR decrease mitochondrial ROS generation and percent free radical leak in rat liver mitochondria, similarly to what has been previously observed in 40% PR and 40% DR. The concentration of complexes I and III, apoptosis inducing factor, oxidative damage to mitochondrial DNA, five different markers of protein oxidation, glycoxidation or lipoxidation and fatty acid unsaturation were also lowered. The results show that 40% isocaloric MetR is enough to decrease ROS production and oxidative stress in rat liver. This suggests that the lowered intake of methionine is responsible for the decrease in oxidative stress observed in DR.

* * *

The abstract really should have specified the measurable oxidation differences in 40% vs. 80% methionine restriction. Are the effects additive, or is there a minimum threshold for positive results, beyond which no further benefits are derived?

It is known that dietary restriction (DR) increases maximum longevity in rodents, but the mechanisms involved remain unknown. Among the possible mechanisms, several lines of evidence support the idea that decreases in mitochondrial oxidative stress and in insulin signaling are involved but it is not known if they are interconnected. It has been reported that when C57BL/6 mice are maintained on an every other day (EOD) feeding their overall food intake is only slightly decreased and plasma insulin-like growth factor (IGF)-1 is even somewhat increased. In spite of this, their maximum longevity is increased, analogously to what occurs in classic DR. Thus, this model dissociates the increase in longevity from the decrease in IGF-1 observed in classic DR. Based on these facts, we have studied the effect of EOD DR on the rate of mitochondrial reactive oxygen species (ROS) production, oxygen consumption, and the percent free radical leak (FRL) of well-coupled liver mitochondria, the marker of mtDNA oxidative damage 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG), the content of complexes I to IV of the respiratory chain, the apoptosis inducing factor (AIF), PGC1-alpha, UCP2, five different markers of oxidative damage to proteins and the full fatty acid composition on C57BL/6 mice liver. It was found that EOD DR decreased ROS production in complex I but not in complex III without changes in oxygen consumption. As a result, FRL was decreased in complex I. Oxidative damage to mtDNA (8-oxodG) and protein oxidation, glycoxidation and lipoxidation were also lower in the EOD restricted group in comparison with the control one while the degree of fatty acid unsaturation was held constant. The EOD group also showed decreases in AIF, PGC1-alpha, and UCP2. These results support the possibility that EOD DR increases maximum life span at least in part through decreases in mitochondrial oxidative stress which are independent from insulin/IGF-1-like signaling.

Previous studies have consistently shown that caloric restriction (CR) decreases mitochondrial reactive oxygen species (ROS) (mitROS) generation and oxidative damage to mtDNA and mitochondrial proteins, and increases maximum longevity, although the mechanisms responsible for this are unknown. We recently found that protein restriction (PR) also produces these changes independent of energy restriction. Various facts link methionine to aging, and methionine restriction (MetR) without energy restriction increases, like CR, maximum longevity. We have thus hypothesized that MetR is responsible for the decrease in mitROS generation and oxidative stress in PR and CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their longevity. We have found, for the first time, that MetR profoundly decreases mitROS production, decreases oxidative damage to mtDNA, lowers membrane unsaturation, and decreases all five markers of protein oxidation measured in rat heart and liver mitochondria. The concentration of complexes I and IV also decreases in MetR. The decrease in mitROS generation occurs in complexes I and III in liver and in complex I in heart mitochondria, and is due to an increase in efficiency of the respiratory chain in avoiding electron leak to oxygen. These changes are strikingly similar to those observed in CR and PR, suggesting that the decrease in methionine ingestion is responsible for the decrease in mitochondrial ROS production and oxidative stress, and possibly part of the decrease in aging rate, occurring during caloric restriction.—Sanz, A., Caro, P., Ayala, V., Portero-Otin, M., Pamplona, R., Barja, G. Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins.

Summary: A group of researchers at Harvard Medical School have been trying to find out what it takes to reach the age of 100 or more.Assuming we're not all knocked off by the genes in our foods, then over the next few years there's going to be an explosion of one group in the population: those aged 100 or more.

A group of researchers at Harvard Medical School have been trying to find out what it takes to reach the age of 100. Is it more than having parents who lived a long time?

The results of the New England Centenarian Study suggest there is a lot more to it than genes. In fact, they've written a book called 'Living to 100: Lessons in Living to your Maximum Potential at Any Age'.

When I was in Boston a couple of weeks ago, I spoke to two of the principal investigators, Drs Margery Silver, a neuropsychologist and Dr Tom Perls, a physician with an interest in the elderly.

Tom Perls: We started of with what we call a population based study of centenarians in which we tried to find all the centenarians in a given geographic area. And we studied them, everything from their biological and medical state of affairs, to how they're doing functionally and what their cognitive status is like and so on. So we just basically tried to get a fair picture of what centenarians are like.

Norman Swan: So who have you got and where do they live?

Tom Perls: We go to these eight towns that are in close proximity of our Division on Ageing here at the Medical School, and basically it turns out that there were about 46 centenarians in this population of about 460,000 people, which comes out being one centenarian per 10,000 people in the population. That's about the going rate for most industrialised countries.

Norman Swan: Is that rate going up?

Tom Perls: It is going up, in fact centenarians are the fastest-growing segment of the population in the United States certainly, and then also probably in Europe. There are several good reasons for that: one is there was a dramatic decrease in childhood related mortality at the turn of the century, with the advent of vaccines and safe water supplies and better public health in general. So a lot of people, who could have gone on to be centenarians, died in their childhood. But now you see all these children living, and these children from the early part of the century are now going on to be today's centenarians.

Norman Swan: So these are really the first beneficiaries, the first real beneficiaries of the hygiene movement in the late 19th century?

Tom Perls: That's right. And the real boom is going to happen of course with people who were born in the 1920s when public health really took off. And of course, with the baby boomers next century when for instance around 2050 or so, we're going to see just a dramatic increase in the number of centenarians.

Norman Swan: Because whilst the problem largely, at least in non-indigenous populations, has been solved in terms of childhood mortality, what's happened since the war is that your life expectancy at say aged 50 has gone up dramatically, it's middle-aged life expectancy that's really gone up.

Tom Perls: That's absolutely right, and we're just seeing much better care of middle-aged and older people in terms of prevention, screening, as well as interventions in terms of major diseases like stroke and cardiovascular disease.

Norman Swan: OK, so you've got this study running of these centenarians. I thought it was more than that, I thought it was about 5,000, it's only 50.

Tom Perls: That's how the study began, with the 50 or so centenarians in this population-based study. But not too long after we started, we began to see that getting to very old age ran in families, and certainly everyone knows the adage 'old age runs in families' but there's been some evidence that maybe that wasn't true among gerontology circles. But here in fact, we were seeing that extreme old age anyway, does run in families. We got very interested in their pedigrees, or their family trees, and that has now - findings from that arm of our research has really thrust us in the direction of looking for genes that explain extreme old age, and now we're conducting an international study where we are looking for centenarians who also have brothers or sisters who achieved extreme old age. And actually looking for the genes that they have in common.

Norman Swan: You showed me a photograph just before we walked in here, of six generations. Just describe those six generations of this one woman's family.

Tom Perls: That was Sarah Knauss' family, who is currently thought to be the oldest woman in the world. Madame Calment died at the age of 122, and now her runner-up, so to speak, is Sarah, who lives out in Pennsylvania in the United States. This photograph that shows up at the end of this magazine, shows her sitting across sitting from her daughter, aged 95.

Norman Swan: Looking very spry, I might add.

Tom Perls: Yes, all of them looking terrific. Followed by her grandson, her great-granddaughter, her great-great-granddaughter, and her great-great-great-grandson.

Norman Swan: She's got all her marbles, she can remember things quite well?

Tom Perls: We actually did visit her with what's called the International Age Validation Committee.

Norman Swan: Proving that she was the oldest woman in the world?

Tom Perls: Well that's right. You know, when you come across somebody that rare, you really have to be very, very careful to make sure that she's the age that she is. And in fact that was done with Madame Calment. -

Norman Swan: Incidentally, Mme Calment is the lady in the South of France who we've actually had on the program, who could remember van Gough coming to her father's office, and the Eiffel Tower being built.

Tom Perls: Right. And despite remembering that, only passed away about a year ago. So we had to go through a similar methodology of proving Sarah's age, and so there was us from the New England Centenarian Study, a representative of the Danish Centenarian Study, a representative of the French Centenarian Study, and a demographer from the University of California, Berkeley, all looking very professorial, and deeming her worthy of the age that she says she is.

Norman Swan: Margery, what sort of questions do you ask of someone to find out what age they are?

Margery Silver: There was no birth certificate, because apparently at that time they did not record the birth. But there were marriage certificates and baptisimal certificates and enough other documents that fitted with the age she says she was, and fitted with the chronology in her family, that it was fairly certain proof.

Norman Swan: And did you test her? You're a neuropsychologist, did you test her?

Margery Silver: We asked her a few questions informally. We have not had permission from the family to test her. However, we are working on that, we would really like to test her, very much.

Norman Swan: Is she still living independently?

Margery Silver: No, she lives in a nursing home. Her 95-year-old daughter, who drove her automobile until about two months ago, just moved into an assisted living right across the street from her. She has fairly severe hearing impairment, but when you ask your questions, if she can hear you, her answers are very appropriate. She's sometimes very funny. At one point she was able to remember her age, part of the date, but not the exact date, and one of the examiners prompted her and she said, 'Oh, well, you know better than I do.'

Norman Swan: Your centenarians, you must have got to know them all pretty much personally.

Margery Silver: Yes, we have. I actually go into their homes to test them, to do the cognitive testing, and the personality testing. So usually I end up sitting at the kitchen table with the centenarian, usually several children, there to oversee things that help me in the testing, because they can often ask questions in a way that are more understandable if the centenarian is hard of hearing, for instance, or if English is a second language. And so it's kind of a family affair, round the kitchen table with grandchildren running in and out, and all kinds of things going on.

Norman Swan: Are they the same sort of person, the same sort of people? Do they have similar personalities? Before we get down to how well they're thinking and remembering, what about their personalities? Is there something about people who live to be 100?

Margery Silver: It's very interesting. The people we studied, the group we studied, is varied, as far as socioeconomic group, as far as ethnic background, but what we have found, our observations and in testing them, we now have some actual data that shows that there is a particular characteristic that is typical of centenarians. And that is that they are able to manage stress very well. And this doesn't mean that they've had stress-free lives. Sometimes you think these people live so long, they must have had really easy lives; some of them have had really very difficult, and even traumatic lives. There are holocaust survivors, there are women who were widowed at an early age and scrubbed floors to raise their children, and yet they seem to have the ability to roll with the punches.

Norman Swan: Flesh that out a bit more for me: they get stressed, how do they respond to it, compared to other people?

Margery Silver: They don't ignore it. For instance, they're very good at handling losses, and they seem to accept their losses, grieve them and then move on. And in many situations solve a problem, recognise it's hard, and then move on. They bounce back.

Norman Swan: They don't fester?

Margery Silver: They don't fester, that's a very good way of putting it.

Norman Swan: Does that mean that sometimes you might superficially think of them as cold, that they're not responding quite emotionally to things as you would expect?

Margery Silver: Oh no, not at all. They're not cold. As I say, they grieve and go on. One wonderful example of this, not from our study, is one of the surviving Delaney Sisters: these are the two sisters in New York -

Norman Swan: Who were the last children of slaves.

Margery Silver: Yes.

Norman Swan: And one just died a day or two ago.

Margery Silver: Yes. And the one who survived has written a book called 'Alone at 107' in which she talks about her grief and about her missing her sister, and it's all out there. And yet at the same time she's making plans to go out and do things, she has plans to write a new book, so she's moving on.

Norman Swan: These were two sisters who lived together most of their lives. One had been a dentist, and one died at the age of 95 leaving the other alone. Neither had married, neither had children.

Margery Silver: Right. Actually they were both over -

Tom Perls: Both lived to be over 100.

Margery Silver: Yes, one was I think 102 when she died. And the surviving one is 107.

Norman Swan: And she spoke about moving on?

Margery Silver: Yes. In fact her book that she wrote says 'Don't worry about me sister Bessie, I got plans'.

Norman Swan: What about their thinking ability?

Margery Silver: Well what we found, which is really optimistic, you know many people, including many scientists, believe that dementia is inevitable if you live long enough. There has been the idea that it increases exponentially in old age, and therefore if you get to be 100 everyone at 100 is going to be demented. And what we've found is that there is a sizeable group of 100-year-olds who are perfectly cognitively intact. And also because many of our subjects agree to donate their brains, we not only have seen that in the neuropsychological testing, but we've seen it in the neuropathological studies, and we've seen very clean, what our neuropathologist calls 'beautiful brains'. Actually we have a slide of the brain of one of our 100-year-old subjects, and the brain of a 52-year-old man with Alzheimer's Disease, and even an untrained eye can see that hers is a 'clean' brain, and that his is filled with the neurofibrillate tangles and plaques of Alzheimer's.

Norman Swan: When you add your groups of people to other people over 100 around the world who are being studied, what sort of percentage figure is it for people who remain intact, as you put it, intellectually?

Margery Silver: In the particular group that we studied in a 'slice of time' we found 21% who were completely cognitively intact, and other who were in a kind of questionable group. In other studies they found, some studies around 25% - 30%, I think one study even up to 40%. Now we're all using different ways of approaching it, and it's a question that needs a lot more research.

Norman Swan: And what percentage living independently?

Margery Silver: About 15% of our centenarians live alone. There's another large group that lives with family, and really would be considered independent in the sense that they do all the things, you know, they dress themselves, they feed themselves, they do all the things that are considered when you look at functioning, physical functioning.

Tom Perls: You know one very important point to make about how they're doing, is how they were doing, as well. Many people have to realise that these centenarians from our respective analysis of the data were completely independent doing things we would equate with 60, 70, 80 year olds, up through their early 90s. And it's only in the last five years or so of their lives where they experience illness. It's what we call a compression of morbidity, where they've lived the vast majority of their lives in excellent health, only to have a short period of time of their lives, at the end of their time, with poor health. And that really is one of the things we're so interested in, and why we study them, is this group either markedly delays, or entirely escapes diseases we normally associate with ageing.

Norman Swan: The key question for those people who would like to live to 100 is, is it simply writ in your genes? You can do a little bit by modifying your lifestyle, but the reality is, if you live to 100, you were actually born to live to 100.

Tom Perls: First of all, the very interesting point to make is a lot of people in the past may have said they'd never want to live to 100. And now what our centenarians are showing people is, my goodness, living to 100 is a wonderful thing to aspire to because look, they have another 30 or 40 years beyond what many people thought was the time to die, of opportunities and possibilities. And they did it because they lived such a long life in good health. They couldn't have gotten to their age in the first place, had they not done that.

Norman Swan: Is there a lower percentage of smokers, and people eating high fat diets? I mean if you were to ask them what they were doing in 1930, they were one of the few people not smoking around, is that the story?

Tom Perls: The story really does boil down to the genes actually. We think that having genes that allow you to both age slowly as well as escape or markedly delay diseases associated with ageing, like Alzheimer's, stroke and cancer, is extremely important to get to 100. A person would need what I would call genetic booster rockets to be able to get to 100. On the other hand, the good news is, people may say 'Well if it's all in the genes, what can I do about it?' but in fact I think that the very good news is that we believe that most people have the genes that will get them to their late 80s in excellent health. The reason that we don't see life expectancies like that on the average, is because people in general take such poor care of themselves. There's a lot of smoking, there's poor diets, the Aussies I know eat a tremendous amount of meat, they love their barbies, and these things, as we know from a lot of epidemiological data, increase mortality rates. If people realise that it was worthwhile to live to older age in good health because of the opportunities and possibilities that our centenarians show that can happen, I'm hoping that they'll spend more time taking better care of themselves exercising, eating appropriately.

Now the centenarians in general, they don't smoke, they never had a history of smoking, it's very rare that you'll find a centenarian with a history of obesity, and so there are some things that even centenarians, despite their wonderful genes, have to do I think, to get to their age. Now Mme Calment is an interesting example. This is the woman who lived to 122. She actually smoked some cigarettes up until the age of 116. Now to me that just says that she really had amazing genes to even to be able to counter the bad effects of smoking, and Lord knows if she didn't smoke she might still be alive today.

Margery Silver: I think there's another point to this centenarian personality, this stress-resistant personality. I do believe that the centenarians probably have a natural temperament that enables them to handle stress well. But we also know that we can all learn to handle stress well, and that one of the things they're telling us, or one of the things that we've learned from them is that it's really important to manage stress well in order to live a long time; that there's a real link with longevity.

Norman Swan: One of the features of getting old is that we blokes don't do it as well as the women. What's the gender split when you get to looking at 100-year-olds, is it all women?

Tom Perls: It isn't all women, but it is pretty dramatic. It's 85% women and 15% men. And so clearly women do get the upper hand on the men at these very old ages. And what's interesting is the men who do get to this very old age, they end up being better off than the women, functionally. And it really speaks for the fact that men who get into their 90s and into their 100s, have to really be in extremely good shape to continue to live at that age. Whereas women, they tend to be physiologically stronger, they can handle living with their diseases. If you give a man and a woman an equal amount of stroke or heart attack, the men will die of it and the women will live with it. So the woman lives with a double-edged sword, of yes, she can live longer but she must also live with diseases associated with ageing. On the other hand, the men, if they do live that long, they really have to be in spectacular shape.

Norman Swan: You, in a forthcoming book, have done some scientific palmistry, in other words questions that you could ask that might predict how long you're going to live. What sort of questions do you ask, is it possible to ask?

Tom Perls: Yes, in our book, 'Living to 100: Lessons in Living to your Maximum Potential at any Age', Margery and I have constructed a life expectancy calculator, and basically what that consists of is about 19 questions which both from our centenarian studies as well as work in public health, really we think make a tremendous difference whether or not a person has the ability to live to very old age. These would certainly be the ones many people would guess, things like whether you smoke or not, stress meat in your diet, or is it more fruit and vegetables. Actually there's some interesting ones that throw people off: for instance, we think flossing your teeth is very important, and we explain -

Norman Swan: Is this because of bugs and heart disease?

Tom Perls: Well that's exactly right. There's been a very strong link between chronic gum disease and the development of what we call immunal complexes that can lead to clogging up the blood vessels that feed the heart. And then there's some questions about your family, that's probably the only thing that you can't necessarily do something about in the questionnaire, which is whether you chose good parents and grandparents. But for the most part these are questions that people can really learn from in terms of modifying their lifestyles to live to an older age. You add up your score from your answers, and before your very eyes, your life expectancy appears before you, and we hope that the questions and the reasons for the questions, help people lead a longer life.

Norman Swan: So you can re-do yourself a year from now and it might have changed?

Tom Perls: That's right.

Norman Swan: I'm not sure I really want to know. Tom Perls, who by the way did part of his gerontology training in Melbourne, who along with Margery Silver runs the New England Centenarian Study at Harvard Medical School.

The book, just to repeat, is called 'Living to be 100: Lessons in Living to your Maximum Potential at any Age' by Tom Perls and Margery Silver. And it's published by Basic Books. It's not out in Australia yet, but you may be able to get it off the web.

And by the way, we've also found that women who have babies late in life live longer. That probably just reflects a young reproductive system.

Giving seniors an appetite for life -- and foodPosted on Thu, Jul. 31, 2008

BY MARY MEEHANMcClatchy News Service

It might just be some vegetable soup, a grilled pimento cheese sandwich and a glass of milk, but 102-year-old Utha B. Deen makes a point to make herself a nice little lunch and supper every day.

Still, her daughter, Betty, frets.

''She's always fussing at me for not eating enough,'' said Deen.

There is a bowl of fresh peaches and bananas in her cozy kitchen, and Deen is likely to cook up a roast and parcel it out in other dishes throughout the week.

Still, like lots of seniors who live on their own, Deen has to be vigilant to make sure she gets proper nutrition. Some of the challenge is cooking for one. Some of it is in response to how the human body changes as we age.

''The metabolic rate slows down,'' said Maria G. Boosalis, director of the division of clinical nutrition at the University of Kentucky College of Health Services. ``The amount of calories we need does go down. Our taste buds don't work as well; we don't smell as well.''

She said older people also tend to have a reduced appetite. Some medicines can change the sense of taste and make you feel less hungry, said Diana Doggett, a Fayette County, Ky., extension agent.

Another issue is dental health. If your teeth aren't healthy, chewing can be a problem and nutrition suffers.

So what can seniors do?

Dietary needs vary depending on age, sex and level of activity. Most seniors need 1,600 to 2,000 calories a day, Boosalis said. Ideally, that would include 1 ½ cups of fruit, 2 cups of vegetables, 5 ounces of grain, three servings of dairy and 5 teaspoons of fat. Getting adequate calcium and vitamin D also is important -- to keep bones strong -- as is a diet high in fiber to keep bowels moving regularly and lower the risk for chronic diseases, such as heart disease and diabetes.

For seniors who might not make it to the grocery as easily or as often as they used to, eating properly can be tough. Although fresh is best, a good alternative can be frozen strawberries or blueberries, with no added sugar, and frozen vegetables. Make sure the pantry has staples including whole grains, peanut butter and shelf-stable milk.

And don't forget about water. As we age, we can experience a decline in the ability to sense thirst, Doggett said.

* * *

Her daughter would do well to quit worrying; not only is that not a trait that will get her mother's age, but it has long been established that reduced caloric intake is likely why her mother is still around and healthy in the first place. You'd think these people would understand that the centenarians are the ones who are doing stuff right!